Our studies aim at elucidating the molecular mechanisms involved in the regulation of gene expression in bacteria and in animal cells. The systems under investigation are the regulation of the lactose operon of E. coli and the mechanism of killing of lymphoma cell lines by glucocorticosteroids. (1) The Lactose Operon: We will pursue the isolation and characterization in vivo of new types of mutants altered either in the structure of the repressor or of the operator in order to define the features of the repressor and of the operator which are important for their interaction. (2) Glucocorticoid Regulation: We will measure the amount and examine the properties of the glucocorticoid receptors of dexamethasone resistant variants of lymphomas. Somatic cell hybridization will be used for complementation and dominance analysis of dexamethasone resistant variants.